Boulanger Y, Chen Y, Commodari F, Senécal L, Laberge A M, Fournier A, St-Pierre S
INRS-Santé, University of Quebec, Pointe-Claire, Canada.
Int J Pept Protein Res. 1995 Jan;45(1):86-95. doi: 10.1111/j.1399-3011.1995.tb01571.x.
The structures of human NPY and of its centrally truncated agonist analog [Ahx5-17]NPY have been investigated in DMSO-d6 by two-dimensional NMR and by molecular modeling. For both peptides, a complete resonance assignment was achieved and a large number (more than 200) of inter-residue NOE connectivities were observed, including long-range connectivities between the N- and C-terminal ends of the chain. Molecular models were calculated using NOE constraints by distance geometry, simulated annealing and conjugate gradient energy minimization. The results indicate that both peptides are folded in the center of their chain, NPY adopting the hairpin shape, whereas the central portion of [Ahx5-17]NPY is characterized by relatively large loops. In contrast to previous models, practically no alpha-helical structure exists for these peptides under our conditions, but two beta-turns are found in NPY and one in [Ahx5-17]NPY. The proximity of the terminal ends could be the determinant factor for their activity.
通过二维核磁共振和分子建模，在氘代二甲基亚砜（DMSO-d6）中研究了人神经肽Y（NPY）及其在中央截短的激动剂类似物[Ahx5-17]NPY的结构。对于这两种肽，均完成了完整的共振归属，并观察到大量（超过200个）残基间的核Overhauser效应（NOE）连接，包括链的N端和C端之间的长程连接。利用NOE约束，通过距离几何、模拟退火和共轭梯度能量最小化计算分子模型。结果表明，两种肽在其链的中央折叠，NPY呈发夹形状，而[Ahx5-17]NPY的中央部分具有相对较大的环。与先前的模型不同，在我们的条件下，这些肽几乎不存在α-螺旋结构，但在NPY中发现两个β-转角，在[Ahx5-17]NPY中发现一个β-转角。末端的接近可能是其活性的决定因素。
